CAREER: Mechanotyping Platform for Studies of Soft Biological Matter

加州大学洛杉矶分校获得了开发高通量机械分型平台（MTP）的奖励。细胞和细胞核的机械特性涉及广泛的生物学背景：它们是决定物理力量如何改变基因表达的核心，更广泛地说，它们可以发出细胞转化的信号。S生理状态，如恶性转化。然而，为了推进我们对细胞/核力学特性机制的基本理解，需要跨越遗传和物理相空间探测细胞和细胞核的力学特性；这需要对大量样品和单个细胞进行测量，而使用现有方法无法在可行的时间尺度上实现。与现有技术相比，MTP在时间、成本和用户可及性方面都有了显著的改进，它由两项独立的技术组成：(1)高通量机械筛选（HTMS）仪器同时探测数百个单独样品的可变形性，方法是使它们受到外部应力，迫使它们通过微米尺度的孔隙变形，并确定传代细胞的数量；这提供了一种生理学相关的检测方法，以检测对细胞通过脉管系统和组织的循环和灌注有直接影响的相对力学变化。(2)机械探测系统（MaPS）以每秒100次的速率直接测量单个细胞和细胞核的弹性模量，方法是让细胞流过微流体通道，用嵌入通道中的力探针戳细胞，并确定由此产生的变形；这将能够以前所未有的速度对单个细胞的机械特性进行重复性测量。拟议的研究将为从干细胞到癌症生物学等领域的生物学研究人员建立一个机械分型的框架。探测细胞的机械特征也可以为分类和治疗多种疾病提供另一种方法。此外，这项研究将为机械表型的分子起源、单细胞群体内的异质性提供关键的见解，更广泛地说，将通过利用单个细胞的固有结构或机械类型来改变生物学研究中关键信息的搜索。这个项目的教育目标是让本科生和高中生以及普通观众参与到使用食物和烹饪作为教学工具的科学中来。用食物来传达复杂的科技概念是一种触感、创新和美味的方法，在促进公众对科学和技术的理解方面被证明是受欢迎和有效的。课程将通过在线模块和互动讲座传播给高中学生，特别是在科学领域代表性不足的群体。本科生将在课堂上通过探究驱动的项目来学习科学，比如设计一个苹果派。公众对科学的理解将通过互动活动来促进，包括科学烘焙大赛。这些教育和推广活动将开创利用食物和烹饪进行多感官科学教育的方法。促进科学和食品知识也解决了美国改善社会经济分层社区饮食和健康问题的迫切需要。更多信息请访问www.scienceandfood.org。

An award is made to UCLA to develop a high throughput Mechanotyping Platform (MTP). Mechanical properties of cells and nuclei are implicated in a wide range of biological contexts: they are central for determining how physical forces alter gene expression, and more broadly they can signal a transformation in a cell?s physiological state, such as in malignant transformation. However, to advance our fundamental understanding of the mechanisms underlying cell/nuclear mechanical properties requires probing the mechanical properties of cells and nuclei across genetic and physical phase space; this demands measurements of a large number of samples and single cells which cannot be achieved on a feasible timescale using existing methods. MTP offers dramatic improvements over current techniques in time, cost, and user-accessibility, and is comprised of two independent technologies: (1) High Throughput Mechanical Screening (HTMS) instrumentation simultaneously probes the deformability of hundreds of individual samples by subjecting them to external stresses, forcing them to deform through micron-scale pores, and determining the number of passaged cells; this provides a physiologically relevant assay to detect relative mechanical changes that have direct implications for the circulation and perfusion of cells through vasculature and tissues. (2) A Mechanical Probing System (MaPS) measures elastic moduli directly from single cells and nuclei at rates of 100 per second by flowing cells through a microfluidic channel, poking the cell with a force probe embedded in the channel, and determining the resultant deformation; this will enable reproducible measurements of the mechanical properties of single cells at unprecedented speeds. The proposed research will establish a framework for mechanotyping that will be accessible to biological researchers in fields ranging from stem cells to cancer biology. Probing the mechanical signatures of cells can also provide an alternative approach to classify and treat a wide range of diseases. In addition, this research will provide critical insight into the molecular origins of mechanical phenotype, heterogeneity within a population of single cells, and more broadly, will transform the search for crucial information in biological research by exploiting the inherent texture or mechanotype of individual cells.The educational objective of this project is to engage undergraduate and high school students, as well as general audiences, in science using food and cooking as pedagogical tools. Communicating sophisticated scientific and technological concepts using food is a tactile, innovative, and tasty approach that is proving to be popular and effective in promoting the public understanding of science and technology. Curricula will be disseminated through online modules and interactive lectures to populations of high school students, especially groups underrepresented in science. Undergraduate students will be engaged in learning science in a classroom setting through inquiry-driven projects, such as engineering an apple pie. The public understanding of science will be promoted through interactive events, including a Scientific Bake-off. These education and outreach activities will pioneer methodologies in multisensoryscience education using food and cooking. Promoting knowledge of science and food also addresses America's pressing need to improve eating and health issues for socio-economically-stratified communities. More information is available at www.scienceandfood.org.